There have been various attempts to administer therapeutic agents to cancerous and precancerous cells in the hope of promoting their apoptotic removal. Generally, these attempts have had limited success because of inadequacies in the delivery means or the agents themselves. For example, many anticancer agent delivery systems lack sufficient specificity to exclusively target cancer cells. Since most anticancer agents strongly interfere with replication and other cellular functions, nonspecific delivery of these agents to noncancerous cells leads to serious toxic side effects.
In particular, the effective delivery of water-soluble low molecular weight anticancer agents is especially difficult because these agents are rapidly cleared from the subject's bloodstream. Similarly, the effective administration of peptide and nucleic acid anticancer agents is difficult because these agents are subject to proteolytic degradation and/or immunogenicity concerns.
Additionally, many current anticancer agents have difficulty crossing, or are unable to cross, the cellular membrane of cancerous cells. Currently, efficient delivery of therapeutic compounds is best achieved with small (typically less than 1,000 Daltons) hydrophobic molecules. However, low molecular weight cytotoxic drugs often localize more efficiently in normal tissues rather than in tumors (K. Bosslet et al., Cancer Res., 58:1195-1201 [1998]) due to the high interstitial pressure and unfavorable blood flow properties within rapidly growing tumors (R. K. Jain, Int. J. Radiat. Biol., 60:85-100 [1991]; and R. K. Jain and L. T. Baxter, Cancer Res., 48:7022-7032 [1998]). Protein and peptide anticancer agents are especially limited in their ability to enter cancer cells. Moreover, even agents that are capable of entering cancer cells often accumulate in the outer layers of tumor tissues and fail to effectively penetrate to the center of solid tumors thus leaving cancer cells at the tumor core to subsequently reseed the subject with new cancers.
In view of the shortcomings in existing drug delivery systems (e.g., compositions), and anticancer drug delivery systems in particular, what are needed are improved drug delivery systems and methods that provide enhanced target specificity and ability to deliver (e.g., translocate) all types of therapeutic agents (e.g.; including hydrophobic, hydrophilic, small, or macromolecular compounds) that are otherwise incapable of entering target (e.g., cancerous) cells and tissues.